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Targeting KRAS in Colorectal Cancer

  • Evolving Therapies (RM Bukowski, Section Editor)
  • Published:
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Abstract

Purpose of Review

Mutations in kirsten rat sarcoma viral oncogene homolog (KRAS) are the most frequently observed genomic alterations in human cancers. No KRAS targeting therapy has been approved despite more than three decades of efforts. Encouraging progress has been made in targeting KRASG12C with KRASG12C specific covalent inhibitors in the past few years. Herein, we review the recent breakthroughs in KRAS targeting.

Recent Findings

KRASG12C mutation was found in 14% of non-small cell lung cancer (NSCLC) and 3% of colorectal cancer. Recently, highly potent KRASG12C specific inhibitors have been developed and demonstrated potent activity in preclinical models. Early results from phase 1 clinical trials with sotorasib and MRTX849 show promising antitumor activity in NSCLC, colorectal cancer and other solid tumors harboring KRASG12C mutation.

Summary

For the first time, the preclinical success of targeting KRAS has translated into clinical benefits, which holds the potential of transforming clinical management of KRAS mutated solid tumors. Additional efforts are needed to identify biomarkers that predict response to KRAS inhibition in patients with KRASG12C as well as to develop strategies to overcome resistance.

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Data Availability

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  1. Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, 1500 E Duarte Rd, Duarte, CA, 91010, USA

    Chongkai Wang & Marwan Fakih

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C.W. and M. F. contributed conception design, literature search and review, writing, graphical design, and editing. All authors read and approved the final manuscript.

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Correspondence to Marwan Fakih.

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Dr. Fakih reports received Honoraria from Amgen and research funding from Astra Zeneca, Amgen and Novartis. Dr. Fakih reports serving as advisory for Amgen, Array, Bayer and Pfizer and as speaker bureau for Amgen and Guardant Health. Chongkai Wang declared no conflict of interests.

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Wang, C., Fakih, M. Targeting KRAS in Colorectal Cancer. Curr Oncol Rep 23, 28 (2021). https://doi.org/10.1007/s11912-021-01022-0

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